Scientists Spot Possible OCD Gene

In Lab Tests, Mice Lacking the SAPAP3 Gene Groom Themselves Compulsively

Medically Reviewed by Louise Chang, MD on August 22, 2007
From the WebMD Archives

Aug. 22, 2007 -- Obsessive-compulsive disorder (OCD) may be affected by a gene called SAPAP3, new research shows.

OCD is an anxiety disorder marked by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions) such as washing hands, counting, checking, or cleaning, which are often performed with the hope of preventing or getting rid of obsessive thoughts, according to background information from the National Institute of Mental Health (NIMH).

The new OCD study, published in tomorrow's edition of the journal Nature, is based on mice bred without the SAPAP3 gene and other mice with a normal SAPAP3 gene.

When the mice were pups, they all behaved normally. But by the time the mice were four to six months old, those lacking the SAPAP3 gene compulsively groomed themselves to the point of self-injury and acted more anxious than normal mice.

"We obviously cannot talk to mice to find out what they are thinking, but these mutant mice clearly did things that looked like OCD," Feng says in a Duke University Medical Center news release.

The scientists tried two strategies to relieve the OCD-like behavior and anxiety in the mice lacking the SAPAP3 gene.

First, they gave some of those mice a daily injection of fluoxetine (the active ingredient in the antidepressant Prozac) for six days. That eased the mice's excessive grooming and anxiety.

The researchers' second strategy involved injecting a bit of DNA, including the SAPAP3 gene, directly into the brains of other mice lacking the SAPAP3 gene. That reduced the mice's anxious and OCD-like symptoms.

The researchers conclude that the SAPAP3 gene may be involved in obsessive-compulsive behavior. But that doesn't rule out other genetic or environmental influences.

The findings "sharpen our focus" on certain brain chemistry circuits involved in OCD, writes Harvard Medical School neurobiology professor Steven Hyman, MD, in a Nature editorial.

But Hyman cautions that studies in mice can't fully mimic OCD.

"In OCD patients, the main cause of anxiety is the unwanted intrusive thoughts. The sufferers are anxious because they cannot be certain that the door is locked, the gas has been turned off, or that they are free of dread microbes. The anxiety-like behaviors observed in these mice may also resemble OCD, but this requires a stretch of the imagination," writes Hyman.

Show Sources

SOURCES: Welch, J. Nature, Aug. 23, 2007; vol 448: pp 894-900. National Institute of Mental Health: "Obsessive-Compulsive Disorder (OCD)." Hyman, S. Nature, Aug. 23, 2007; vol 448: pp 871-872. News release, Duke University Medical Center. News release, National Institute of Neurological Disorders and Stroke. News release, Nature.

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